• Approval by: DTC Approval Date
  • 1 mL/h = 10 nanogram/kg/minute.
  • 1 mL/h = 50 nanogram/kg/minute.
  • Original version Date: 15/04/2019




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    Original version Date: 15/04/2019

    Author: NMF Consensus Group

    Current Version number: 1

    Current Version Date: 15/04/2019

    Risk Rating: Low

    Due for Review: 15/04/2024

    Approval by: DTC

    Approval Date:


    Prostaglandin E1(Alprostadil)


    Revision Date : 28/10/2019

    Approved: TC, KOH




    Alert

    1 microgram = 1000 nanograms.

    Indication


    For temporary maintenance of ductus arteriosus patency until corrective or palliative surgery can be performed in neonates with ductal-dependent congenital heart defects.

    Action

    Relaxes the ductus arteriosus in early postnatal life and supports its patency.

    Drug Type

    Prostaglandin E1 or PGE1

    Trade Name

    Prostin VR.

    Presentation

    Ampoules (sterile solution) 500 microgram/mL 1 mL

    Dosage / Interval


    Starting Dose

    Dose: 10 nanogram/kg/minute (range: 5 to 50 nanogram/kg/minute).


    For known congenital heart disease patients and prior to ductal closure: Start at 10 nanogram/kg/min.

    If there is no clinical or echocardiographic response to the maximum dose of 50 nanogram/kg/min, then consult a paediatric cardiologist. Very rarely they may suggest a very short trial of up to 100 nanogram/kg/min.


    Maintenance Dose

    3-20 nanogram/kg/minute. Aim is to be on the lowest dose that safely maintains ductal patency.



    Maximum dose

    Higher doses ≥50 nanogram/kg/minute may be needed to resuscitate infants with poor perfusion and oxygenation (‘grey baby’) and with ductal closure in suspected duct-dependent congenital heart disease.

    Route

    Continuous IV infusion.

    Preparation/Dilution

    LOW concentration continuous IV infusion [use if attempting to avoid ventilation and keep ductus open]

    Infusion strength

    Prescribed amount

    1 mL/hour = 10 nanogram/kg/minute

    30 microgram/kg alprostadil (Prostin VR, PGE1) and make up to 50 mL

    First dilution: Draw up 1 mL (500 microgram) of alprostadil and add 9 mL of sodium chloride 0.9% or glucose 5% to make a final volume of 10 mL with a concentration of 50 microgram/mL.

    Second dilution: From this, draw up 0.6 mL/kg (30 microgram/kg) and dilute to 50 mL with sodium chloride 0.9% or glucose 5%. Infuse at rate of 1 mL/h = 10 nanogram/kg/minute.


    HIGH concentration continuous IV infusion [consider if ductus closed and/or mechanically ventilated]

    Infusion strength

    Prescribed amount

    1 mL/hour = 50 nanogram/kg/minute

    150 microgram/kg alprostadil (Prostin VR, PGE1) and make up to 50 mL

    First dilution: Draw up 1 mL (500 microgram of alprostadil) and add 9 mL of sodium chloride 0.9% or glucose 5% to make a final volume of 10 mL with a concentration of 50 microgram/mL.

    Second dilution: From this, draw up 3 mL/kg (150 microgram/kg) and dilute to 50 mL with sodium chloride 0.9% or glucose 5%. Infusing at rate of 1 mL/h = 50 nanogram/kg/minute.



    Administration

    Continuous intravenous infusion. Ensure reliable intravenous access as short half-life.

    Monitoring


    Continuous pulse oximetry, heart rate, ECG and blood pressure monitoring.
    Assess urine output and peripheral perfusion frequently.

    Contraindications




    Precautions

    Ensure adequate cardiorespiratory monitoring and cardiorespiratory resuscitation equipment available for immediate use if necessary.

    Apnoea is frequent. Commencement of alprostadil ≤ 20 nanogram/kg/min and low maintenance dose reduces apnoea incidence.

    Titrate to infant’s response (increased oxygenation, echo findings and side effects) - Aim is to be on the lowest dose that safely maintains the ductal patency.

    Hyperosmolar – infuse at concentrations < 20 microgram/mL.

    Neonates with total anomalous pulmonary venous return below the diaphragm – may precipitate pulmonary oedema because of increased pulmonary blood flow.


    Drug Interactions

    Concomitant administration with heparin may result in an increased risk of bleeding.

    Adverse Reactions


    Apnoea is frequent. Commencement of alprostadil ≤ 20 nanogram/kg/min and low maintenance dose reduces apnea incidence. Methylxanthines (caffeine or aminophylline) may be used to prevent or treat apnoea. [4]

    May lower blood pressure by relaxing the vascular smooth muscle causing vasodilatation and can elevate body temperature.

    Other reported effects include abdominal distension, bradycardia, enterocolitis, vomiting and skin rash. [5]

    With prolonged use, skeletal changes [10] and hypertrophic pyloric stenosis [11, 12] have been reported.

    Extravasation may cause tissue necrosis.


    Compatibility


    Fluids: Glucose 5%, sodium chloride 0.9%.

    Y-site: Amino acid solutions, ampicillin; cefazolin; cefotaxime; chlorothiazide; dobutamine; dopamine; fentanyl; gentamicin; methylprednisolone; nitroprusside; potassium chloride; tobramycin, vancomycin; vecuronium.


    Syringe: Caffeine; dobutamine; dopamine; adrenaline (epinephrine); fentanyl; midazolam; morphine.

    Incompatibility

    Y-site: Levofloxacin

    Stability

    Diluted solution stable for up to 24 hours.

    Storage

    Ampoule: Store at 2 to 8°C. Do not freeze.

    Special Comments


    Do not use if cloudy (crystallised).

    Undiluted solution (500 microgram/mL) is hyperosmolar. Dilute before administration to a concentration of 20 microgram/mL or less.



    Evidence summary

    Efficacy:


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